Monoclonal antibodies demonstrate impressive response rates in lymphoid diseases, and treatment indications are expanding. Both alemtuzumab(Drug information on alemtuzumab) (Campath) (anti-CD52) and rituximab(Drug information on rituximab) (Rituxan) (anti-CD20) are active in chronic lymphocytic leukemia (CLL) and low-grade lymphomas. However, activity in some sites (lymph nodes, liver, spleen) is limited. Here, we explore the safety and efficacy of a combination of alemtuzumab and rituximab in patients with relapsed/refractory hematologic malignancies expressing CD52 and CD20.
Rituximab was given at a dose of 375 mg/m² IV every week × 4 doses. Alemtuzumab was given at a dose of 3, 10, and 30 mg IV on days 3, 4, and 5 of week 1, respectively. During weeks 2 through 4, alemtuzumab was given at a dose of 30 mg IV on days 3 and 5 of each week (total of seven 30-mg doses). Trimethoprim(Drug information on trimethoprim) and sulfamethoxazole(Drug information on sulfamethoxazole) and valacyclovir (Valtrex) were given for prophylaxis.
A total of 31 patients have been treated (18 CLL, 8 CLL/prolymphocytic leukemia [PLL], 2 Richter’s syndrome, 3 mantle cell lymphoma). The median age is 60 years (range: 42-79 years). The median number of previous treatments is 4 (range: 1-8); 17/29 patients (59%) were refractory to fludarabine, 18/28 (64%) to alkylators, and 14/27 (52%) to both; and 23/31 patients (74%) were Rai stage ³ 3. The median beta-2-microglobulin level was 5.3 mg/dL (range: 2.4-15.8 mg/dL). Five patients (2 CLL, 3 CLL/PLL) received two courses.Toxicities were mainly grade 1/2 and infusion-related. Most frequently observed were fevers and rigors (up to 97% of patients), dyspnea (52%), rash/hives (42%), fatigue (39%), myalgias (35%), and nausea/vomiting (23%). Responses by site (³ 50% improvement at each site) are given below:
By National Cancer Institute response criteria, 3 patients achieved a complete response (2 CLL, 1 CLL/PLL), 10 patients a partial response (7 CLL, 3 CLL/PLL), and 1 patient a nodal partial response (CLL), for an overall response rate of 45% (14/31 patients). Among responders, the median time to progression was 7 months (range: 1-12 months) and the median survival was 9 months (range: 3-13 months). Infections occurred in 15/31 patients, including 5 cytomegalovirus (CMV) antigenemia, 5 pneumonia (1 viral, 2 fungal, 1 bacterial), 1 skin, and 7 fever of unknown origin.
CONCLUSION: We conclude that the combination of alemtuzumab and rituximab in this schedule is safe and shows encouraging activity in a poor-prognosis group of patients.